Intratumoral interleukin-9 delineates a distinct immunogenic class of gastric cancer patients with better prognosis and adjuvant chemotherapeutic response.
Intratumoral interleukin-9 delineates a distinct immunogenic class of gastric cancer patients with better prognosis and adjuvant chemotherapeutic response.
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瘤内白细胞介素 9 描绘了具有更好预后和辅助化疗反应的独特免疫原性类别的胃癌患者
DOI：
10.1080/2162402x.2020.1856468
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发表时间：
2020-12-15
期刊：
影响因子：
7.2
通讯作者：
Shen Z
中科院分区：
文献类型：
--
作者：
Fang H;Li R;Gu Y;Fei Y;Jin K;Chen Y;Cao Y;Liu X;Lv K;Wang J;Yu K;Lin C;Liu H;Li H;He H;Zhang W;Zhang H;Shen Z
白细胞介素-9（IL-9）是一种与炎症和变态反应相关的T细胞因子，但IL-9在胃癌中的表达水平及其临床意义尚不明确。我们的研究旨在揭示IL-9在胃癌进展中的关键作用。在此，共453例接受根治性切除术的胃癌患者入选进行免疫组化分析，并进行Kaplan-Meier分析以比较不同亚组患者的总生存期。我们通过流式细胞术进一步研究了IL-9表达与肿瘤内CD 8 + T细胞功能状态之间的相关性。体外实验进一步探讨IL-9对抗肿瘤免疫的影响。结果表明，高表达IL-9的胃癌患者总体生存率提高，并从5-氟尿嘧啶为基础的辅助化疗（ACT）中获益更多。高IL-9表达与肿瘤内CD 8 + T细胞数量增加和功能升高相关。体外研究表明，重组人IL-9（rhIL-9）通过增强肿瘤内CD 8 + T细胞的功能发挥抗肿瘤活性。此外，我们发现rhIL-9可以增强Pembrolizumab在胃癌中的疗效。总之，这些结果表明，IL-9的表达可以作为一个独立的预测总生存期和ACT反应和增强IL-9信号转导可能是一个重要的治疗策略，在胃癌。
Interleukin-9 (IL-9) is a T cell cytokine that is associated with inflammation and allergy, but the expression level of IL-9 in gastric cancer and its clinical significance are less well established. Our study aims to uncover the critical role of IL-9 in the progression of gastric cancer. Here, a total of 453 patients with gastric cancer undergoing curative resection were enrolled for immunohistochemical analyses, and Kaplan-Meier analysis was conducted to compare overall survival of patients in different subgroups. We further investigated the correlation between IL-9 expression and functional status of intratumoral CD8+ T cells by means of Flow cytometry. Moreover, in vitro study was preformed to further explore the influence of IL-9 on anti-tumor immunity. Results indicated that gastric cancer patients with high IL-9 expression showed improved overall survival and gained more benefit from 5-fluorouracil-based adjuvant chemotherapy (ACT). High IL-9 expression was associated with increased numbers and elevated function of intratumoral CD8+ T cells. In vitro study revealed that recombinant human IL-9 (rhIL-9) exhibit anti-tumor activity via enhancing the function of intratumoral CD8+ T cells. Moreover, we found rhIL-9 could augment the efficacy of Pembrolizumab in gastric cancer. In summary, these results suggest that IL-9 expression could act as an independent predictor for overall survival and ACT response and enhancing IL-9 signaling might represent an important therapeutic strategy in gastric cancer.